One of the therapeutic methods for cancers (malignant neoplasms), an intractable disease, includes so-called cancer immunotherapy which causes regression of cancer cells by utilizing an immune system of individual patients. The important point in this method is how to make the immune system recognize the cancer cells as foreign and induce immune cells that are aggressive to the cancer cells.
Key immune cells involved in antitumor immunity include a cytotoxic T cell expressing cell surface protein CD8 (CD8-positive T cell) and a T cell expressing cell surface protein CD4 (CD4-positive T cell). CD8-positive T cells are those that, when activated, lyse a cell presenting antigens bound to an HLA class I molecule. CD4-positive T cells are cytokine-secreting Th cells, which, upon being activated by macrophages and/or dendritic cells which present antigens on HLA class II molecules, exert a helper function for inducing and maintaining CD8-positive T cells.
Th cells are known to be classified by the type of cytokine that they secrete into Th1 cells (producing IFN-γ or the like), Th2 cells (producing IL-4 or the like), and Th0 cells (having a low cytokine-producing ability or producing both IFN-γ and IL-4), and the roles of each cell are now being elucidated. CD4-positive T cells can be provided with an effector function by their indirect mechanism against MHC class II molecule-negative tumors (MHC class II-tumors) via, for example, activation of macrophages or by their direct mechanism against MHC class II-positive tumors.
Previous studies of T cells in human cancer immunotherapy have mainly focused on identification and induction of CD8-positive HLA class I restricted CTL response (Patent Document 1). As for CD4-positive T cells, tyrosinase, a cancer antigen; the identification of its epitope to CD4-positive T cells; and some other epitopes have been reported (Patent Document 2), but the number of reports on CD4-positive T cells is much smaller than that on CD8-positive HLA class I restricted peptide.
Reported tyrosinase, which is expressed in normal and tumor cells of the melanocyte lineage and shown to be a specific target of CD4-positive melanoma-reactive T cells, is the only melanoma-associated and tissue-specific antigen that binds to MHC class II molecules (Non-Patent Document 1). However, since tyrosinase is expressed only in limited types of tumors, it can hardly be said to be a promising cancer antigen in cancer immunotherapy.
A gene, referred to as Survivin, which encodes tumor-specific antigens that can be recognized by CD8-positive T cells has recently been reported (Non-Patent Document 2). Survivin is a 142-amino acid residue protein identified as a substance that inhibits apoptotic action. It has been reported that Survivin is distinctively characterized by its upregulated expression in limited normal tissues such as fetal tissues, and thymus and testis of adult; and in tumor tissues, particularly tumorigenic lung, colon, mammary gland, spleen, prostate gland, and lymphoma (Non-Patent Document 2).
Survivin, upregulated expression of which has also been reported to correlate with poor prognosis of neoplastic diseases, is considered to be a protein that plays a very important role as a tumor antigen, and the identification of MHC class II restricted peptide in Survivin has been carried out (Non-Patent Document 3). However, since the peptide reported in Non-Patent Document 3 restricts limited HLA types of HLA class II, it is necessary to use multiple peptides, which are applicable to more HLA types, to be clinically available.    Non-Patent Document 1    Topalian, S. L. et al., 1994, Proc. Natl. Acad. Sci. USA, Vol. 91, pp. 9461-9465    Non-Patent Document 2    Chiara Casati et al., CANCER RESEARCH, 2003, Vol. 63, pp. 4507-4515    Non-Patent Document 3    Matthias Piesche et al., Human Immunology, 2007, Vol. 68, pp. 572-576    Patent Document 1    WO95/19783    Patent Document 2    WO97/11669